Benzyl Bromide → Dibenzyl ether

HRID 2103384Notes

Reaction equation

HRID 2103384 reaction equation
O[C@H]1CN([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=O)[C@H](C(OC)=O)C1.[H-].[Na+].C(Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH2:10]([O:9][CH2:7][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 6884112-Methyl 1-(phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

Product 1

HCID 7657Dibenzyl etherYield 90%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1-Benzyl 2-methyl (2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate (6.60 g, 23.6 mmol) was dissolved in dry THF (100 mL) and cooled to 0° C. under nitrogen. Sodium hydride (1.04 g, 26.0 mmol, 60% dispersion in mineral oil) was added in portions and the mixture was stirred for 15 minutes. Tetra-n-butylammonium iodide (0.40 g, 1.0 mmol) and benzyl bromide (3.15 mL, 26.0 mmol) were added and the mixture stirred for one hour at 0° C. and then one hour at room temperature. The mixture was diluted with ethyl acetate. The organic layer was washed with water and then brine, dried over MgSO4, filtered, and concentrated. The residue was chromatographed on silica gel (20% to 50% ethyl acetate/hexane) to give 4.21 g (48%) of benzyl ether. LC/MS (M+H)+ m/z=370.2; 1H NMR (CDCl3) δ 7.34 (m, 10H), 5.13 (m, 2H), 4.51 (m, 3H), 4.20 (m, 1H), 3.68 (m, 2H), 3.54 and 3.78 (s, 3H), 2.45 (m, 1H), 2.11 (m, 1H).

Workup

  1. stirringthe mixture stirred for one hour at 0° C.
  2. customone hour
  3. customat room temperature
  4. washThe organic layer was washed with water
  5. dry with materialbrine, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel (20% to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-40bb206476094901947bee4fad5bcbeb
Source dataset
uspto-grants-2009_08
Patent number
US07576089B2

Reaction notes

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